Analyses of Foxp3⁺ Treg cells and Tr1 cells in subcutaneous immunotherapy-treated allergic individuals in humans and mice

Abstract

Subcutaneous immunotherapy (SCIT) is a causative treatment for allergic diseases. More recently, it has become clear that regulatory T (Treg) cells are increased by SCIT. Treg cells are generally divided into two main groups: 1) CD25⁺ Foxp3⁺ CD4⁺ T cells (Foxp3⁺ Treg cells) and 2) IL-10-producing Foxp3⁻ CD4⁺ T cells (Tr1 cells). We demonstrated that the number of Tr1 cells in peripheral blood mononuclear cells in SCIT-treated pollinosis patients were significantly higher than that in non-SCIT-treated patients, but Foxp3⁺ Treg cells were not. Consistent with the results of human peripheral blood, Tr1 cells were increased in the lungs of asthmatic mice by SCIT, but Foxp3⁺ Treg cells were not. Moreover, in vitro-induced Tr1 cells were responded to the antigen to produce a large amount of IL-10 in in vitro and in vivo. Adoptive transfer of the induced Tr1 cells significantly suppressed the development of asthma. In any species of human and mouse, the increase in Tr1 cells rather than Foxp3⁺ Treg cells could be important for the effects of SCIT. The increased Tr1 cells by SCIT functionally suppressed allergic asthma probably via production of IL-10 in response to the specific antigen. Therefore, analyses of the induction mechanisms of Tr1 cells and search for compounds which induce Tr1 cells are thought to lead to development of more efficient SCIT.